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A behavioral memory's lifetime represents multiple molecular lifetimes, suggesting the necessity for a self-perpetuating signal. One candidate is DNA methylation, a transcriptional repression mechanism that maintains cellular memory throughout development. We found that persistent, gene-specific cortical hypermethylation was induced in rats by a single,(More)
Linkage analysis was used to search the genome for chromosomal regions harboring familial Alzheimer's disease genes. Markers on chromosome 14 gave highly significant positive lod scores in early-onset non-Volga German kindreds; a Zmax of 9.15 (theta = 0.01) was obtained with the marker D14S43 at 14q24.3. One early-onset family yielded a lod score of 4.89(More)
Previous studies have suggested that in some circumstances, learning processes such as overshadowing may determine the effects that one drug has upon the response to another. The experiments described here examined overshadowing in rats trained to discriminate mixtures of nicotine plus midazolam in two-lever operant procedures with food reinforcement. After(More)
The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset < 60 years), and late-onset families. A genetic association was observed between apolipoprotein E (ApoE) allele epsilon 4 and(More)
Generalization to different drugs and drug mixtures has been examined in rats trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with(More)
RATIONALE Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and studies on single drugs with multiple effects. OBJECTIVE This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations. METHODS Rats were trained to discriminate a(More)
Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and to studies on single drugs with multiple effects. The experiments described here investigated whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations. Rats were trained to discriminate a mixture of nicotine (0.4(More)
Drug discrimination methods that entail training with mixtures of drugs may shed light on polydrug abuse and on the actions of single drugs that interact with more than one receptor. In AND-discrimination procedures (drug A + drug B vs. vehicle), mixtures are discriminated primarily on the basis of their component drugs: these discriminations may be useful(More)
It has been suggested that use of the AND-OR training method may be associated with an enhancement of the pharmacological specificity of discriminations based on mixture of drugs. Rats were trained to discriminate a mixture of nicotine (0.4 mg/kg s.c.) plus midazolam (0.2 mg/kg s.c.) from saline (AND-discrimination, n = 8) or to discriminate the mixture(More)
A gene for early-onset familial Alzheimer's disease (FAD) is located on chromosome 14q24.3. The c-fos gene (FOS) is also located in the same band of this chromosome and is thus a candidate for the FAD locus. A yeast artificial chromosome (YAC) clone was identified which contains FOS. This YAC also contains the short-tandem repeat polymorphic (STRP) locus(More)
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